Modulation of integrin activation by an entropic spring in the β-knee.

Citation:

Smagghe, B., Huang, P., Ban, Y.-E., Baker, D. & Springer, T.A. Modulation of integrin activation by an entropic spring in the β-knee. J Biol Chem. 285, 43, 32954-66 (2010).
Smagghe_2010_19285.pdf1.55 MB

Abstract:

We show that the length of a loop in the β-knee, between the first and second cysteines (C1-C2) in integrin EGF-like (I-EGF) domain 2, modulates integrin activation. Three independent sets of mutants, including swaps among different integrin β-subunits, show that C1-C2 loop lengths of 12 and longer favor the low affinity state and masking of ligand-induced binding site (LIBS) epitopes. Shortening length from 12 to 4 residues progressively increases ligand binding and LIBS epitope exposure. Compared with length, the loop sequence had a smaller effect, which was ascribable to stabilizing loop conformation, and not interactions with the α-subunit. The data together with structural calculations support the concept that the C1-C2 loop is an entropic spring and an emerging theme that disordered regions can regulate allostery. Diversity in the length of this loop may have evolved among integrin β-subunits to adjust the equilibrium between the bent and extended conformations at different set points.

Last updated on 09/30/2015